Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0154316
Title: Phase I study of oral vinorelbine in combination with erlotinib in advanced non-small cell lung cancer (NSCLC) using two different schedules
Authors: Sutiman N.
Zhang Z.
Ang M.K. 
Tan S.-W.D.
Toh C.K.
Ng Q.S.
Chowbay B. 
Lim W.-T. 
Keywords: erlotinib
navelbine
antineoplastic agent
erlotinib
OSI-420
quinazoline derivative
vinblastine
vinorelbine tartrate
adult
advanced cancer
aged
alopecia
anemia
anorexia
area under the curve
arthralgia
Article
cancer fatigue
clinical article
clinical effectiveness
constipation
controlled study
diarrhea
dizziness
drug dose escalation
drug efficacy
drug response
drug safety
drug tolerability
dry eye
dry skin
dysphagia
face pain
febrile neutropenia
female
heartburn
human
hyponatremia
infection
keratitis
loss of appetite
male
maximum plasma concentration
myalgia
nail disease
nausea
neuropathy
neutropenia
non small cell lung cancer
nose disease
outcome assessment
paronychia
phase 1 clinical trial
pruritus
rash
steady state
stomatitis
vomiting
analogs and derivatives
Carcinoma, Non-Small-Cell Lung
clinical trial
drug administration
middle aged
treatment outcome
Adult
Aged
Antineoplastic Combined Chemotherapy Protocols
Carcinoma, Non-Small-Cell Lung
Drug Administration Schedule
Erlotinib Hydrochloride
Female
Humans
Male
Middle Aged
Quinazolines
Treatment Outcome
Vinblastine
Issue Date: 2016
Citation: Sutiman N., Zhang Z., Ang M.K., Tan S.-W.D., Toh C.K., Ng Q.S., Chowbay B., Lim W.-T. (2016). Phase I study of oral vinorelbine in combination with erlotinib in advanced non-small cell lung cancer (NSCLC) using two different schedules. PLoS ONE 11 (5) : e0154316. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0154316
Abstract: Purpose: This study aimed to evaluate the safety, tolerability and pharmacokinetics of the combination of oral vinorelbine with erlotinib using the conventional (CSV) and metronomic (MSV) dosing schedules in patients with advanced non-small cell lung cancer (NSCLC). Methods: This was an open-label, multiple dose-escalation phase I study. An alternating 3+3 phase I design was employed to allow each schedule to enroll three patients sequentially at each dose level. Thirty patients with Stage IIIB/IV NSCLC were treated with escalating doses of oral vinorelbine starting at 40 mg/m 2 on day 1 and 8 in the CSV group (N = 16) and at 100 mg/week in the MSV group (N = 14). Erlotinib was administered orally daily. Results: The maximum tolerated dose was vinorelbine 80 mg/m 2 with erlotinib 100 mg in the CSV group and vinorelbine 120 mg/week with erlotinib 100 mg in the MSV group. Grade 3/4 toxicities included neutropenia (N = 2; 13%) and hyponatremia (N = 1; 6%) in the CSV group, and neutropenia (N = 5; 36%) in the MSV group. Objective response was achieved in 38% and 29% in the CSV and MSV groups respectively. Vinorelbine co-administration did not significantly affect the pharmacokinetics of erlotinib and OSI-420 after initial dose. However, at steady-state, significantly higher C max , higher C min and lower CL/F of erlotinib were observed with increasing dose levels of vinorelbine in the CSV group. Significantly higher steady-state C min , C avg and AUC ss of erlotinib were observed with increasing dose levels of vinorelbine in the MSV group. Conclusions: Combination of oral vinorelbine with erlotinib is feasible and tolerable in both the CSV and MSV groups. Trial Registration: ClinicalTrials.gov NCT00702182. © 2016 Sutiman et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/161571
ISSN: 19326203
DOI: 10.1371/journal.pone.0154316
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